The development of innovative approaches to deliver medications has been growing now for the last few decades and generates a growing interest in the dermatopharmaceutical field. Transdermal drug delivery in particular, remains an attractive alternative route for many therapeutics. However, due to the limitations posed by the barrier properties of the stratum corneum, the delivery of many pharmaceutical dosage forms remains a challenge. Most successful therapies using the transdermal route have been ones containing smaller lipophilic molecules with molecular weights of a few hundred Daltons. To overcome these limitations of size and lipophilicity of the drugs, transferosomes have emerged as a successful tool for transdermal delivery of a variety of therapeutics including hydrophilic actives, larger molecules, peptides, proteins, and nucleic acids. Transferosomes exhibit a flexible structure and higher surface hydrophilicity which both play a critical role in the transport of drugs and other solutes using hydration gradients as a driving force to deliver the molecules into and across the skin. This results in enhanced overall permeation as well as controlled release of the drug in the skin layers. Additionally, the physical–chemical properties of the transferosomes provide increased stability by preventing degradation of the actives by oxidation, light, and temperature. Here, we present the history of transferosomes from solid lipid nanoparticles and liposomes, their physical–chemical properties, dermal kinetics, and their recent advances as marketed dosage forms.This article is categorized under: Biology‐Inspired Nanomaterials > Lipid‐Based Structures Therapeutic Approaches and Drug Discovery > Emerging Technologies

Oxcarbazepine (OXC) is an anticonvulsant drug, indicated for the treatment of the neurological disorder, epilepsy. The objective of the present study was to evaluate the transdermal delivery of OXC from microemulsions using different penetration enhancers. Transcutol^® P (TRC), oleic acid (OA), cineole (cin), Labrasol (LS), Tween 80 (T80) and N-Methyl-Pyrrolidone (NMP) were used as penetration enhancers as well as microemulsion components. Simple formulations of OXC in propylene glycol (PG) incorporating various penetration enhancers and combination of penetration enhancers were also evaluated for transdermal delivery. Drug delivery and penetration enhancement were studied using human cadaver skin on Franz diffusion cells. The results showed that all penetration enhancers improved the rate of permeation of OXC compared to the control. The flux of drug delivery from the various formulations was found to be, in decreasing order, cin > OA + TRC > NMP > TRC > OA. Overall, microemulsions prepared using cineole, Tween 80 and Transcutol^® P (TRC) were shown to be provide the best penetration enhancement for OXC.

The bioactive compound, thymoquinone (TQ), found in Nigella sativa seeds is known for its various therapeutic properties. Thymoquinone (TQ), a bioactive compound found in Nigella sativa seeds, is known for its various therapeutic properties. However, TQ as a compound is challenging for a pharmaceutical formulator due to its hydrophobic nature and chemical instability, limiting its skin penetration. Transethosomes, as a formulation, provide an environment that enhances the solubility of TQ, stability, as well as skin permeation. To optimize TQ transethosomal formulations, we introduced a combination of surfactants namely nonionic Tween 20 and ionic sodium lauryl sulfate (SLS) or sodium lauroyl glutamate (SLG). These surfactants stabilize the formulation, reduce aggregation, and improve biocompatibility, as well as minimizing potential toxicity. Using the Langmuir monolayer technique, we fine-tuned the formulation composition and gained insights into its interfacial behavior. We conducted skin penetration studies using Rhodamine B as a model lipophilic compound to understand the skin penetration mechanisms. Our findings revealed that the transethosomes formulation, a combination of ionic and nonionic surfactants in the F2 formulation, resulted in the smallest particle sizes (115.4 nm) and demonstrated the highest skin permeation after 24 hours (267.13 μg/cm²), surpassing the control and ethosomal formulations. Additionally, this transethosomal formulation exhibited antimicrobial activity against S. aureus, with a zone of inhibition of 26.4 ± 0.3 mm. Importantly, we assessed the cytotoxicity of both ethosomes and transethosomes at concentrations ranging from 3.5 μM to 50 μM on HaCaT cell lines and found no cytotoxic effects in comparison to TQ solution controls. These results suggest the potential safety and efficacy of these TQ formulations and their further development in skin delivery.

Transdermal drug delivery offers several advantages over conventional routes. However, its use is limited by the low permeability of the stratum corneum. This limitation is especially significant in the case of hydrophilic drugs such as caffeine. This study explored microemulsion systems to enhance the transdermal delivery of caffeine (CF) using chemical penetration enhancers as cosurfactants. Kolliphor^® PS80 (PS80), Kolliphor^® RH40 (RH40), Kolliphor^® PS20 (PS20), and Kollicream^® OD (OD) were evaluated as cosurfactants for the first time in microemulsion formulations consisting of water, oil, and a fixed surfactant-to-cosurfactant ratio of 4:1 (w/w), with 14% of each cosurfactant incorporated. CF skin permeation from microemulsions was assessed via in vitro permeation studies using Franz diffusion cells and human cadaver skin. The results showed that OD-based microemulsions achieved approximately 3-fold higher CF skin permeation compared with the control formulation and 1.4–1.6-fold higher permeation compared with formulations containing PS80, RH40, and PS20. Furthermore, CF solubility in the four cosurfactants followed the order: PS20 > RH40 > PS80 > OD. These findings indicate that PS20 provides the highest solubility for CF among the tested cosurfactants. The results also included visual evaluations. No significant changes in appearance or physical properties were observed during the 10-month study. All samples remained clear and stable throughout the testing period. This study uniquely highlights the critical role of cosurfactant selection in optimizing microemulsion-based transdermal delivery systems. This work addresses a previously unexplored aspect, namely, the effect of cosurfactants with different physicochemical properties on the skin permeation of caffeine. The findings provide valuable insight into developing more effective transdermal and topical drug delivery systems.